5565. Lonafarnib

Nomenclature

CAS number: 193275-84-2
4-[2-[4-[(11R)-3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxamide; Sch-66336; Sarasar (Schering-Plough).
C27H31Br2ClN4O2; mol wt 638.82.
C 50.76%, H 4.89%, Br 25.02%, Cl 5.55%, N 8.77%, O 5.01%.

Description and references

Tricyclic farnesyl protein transferase inhibitor. Prepn: R. J. Doll et al., WO 9723478; eidem, US 5874442 (1997, 1999 both to Schering-Plough); F. G. Njoroge et al., J. Med. Chem. 41, 4890 (1998). Improved prepn: S.-C. Kuo et al., J. Org. Chem. 68, 4984 (2003). Crystal structure of complex with farnesyl protein transferase: C. L. Strickland et al., J. Med. Chem. 42, 2125 (1999). LC/MS/MS determn in plasma: N. M. G. M. Appels et al., Rapid Commun. Mass Spectrom. 19, 2187 (2005). Antitumor activity in human xenograft and transgenic mouse cancer models: M. Liu et al., Cancer Res. 58, 4947 (1998). Clinical evaluation in cancer: A. A. Adjei et al., ibid. 60, 1871 (2000). Inhibition of P-glycoprotein mediated drug efflux: E. Wang et al., ibid. 61, 7525 (2001). Clinical evaluation with paclitaxel in non-small cell lung cancer: E. S. Kim et al., Cancer 104, 561 (2005). Review of development and clinical experience: F. Morgillo, H.-Y. Lee, Expert Opin. Invest. Drugs 15, 709-719 (2006).

Chemical structure

Properties

White solid. Crystals from acetone, mp 214.5-215.9° (monohydrate); anhydrous form mp 222-223°. [α]D25 = +49.1° (c = 0.21 in methanol).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Farnesyl Transferase Inhibitors